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B cell-specific knockout of AID protects against atherosclerosis.
Ebrahimian, Talin; Dierick, France; Ta, Vincent; Kotsiopriftis, Maria; O'Connor Miranda, Jonathan; Mann, Koren K; Orthwein, Alexandre; Lehoux, Stephanie.
Affiliation
  • Ebrahimian T; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada. talin.ebrahimian@mcgill.ca.
  • Dierick F; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • Ta V; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • Kotsiopriftis M; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • O'Connor Miranda J; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • Mann KK; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • Orthwein A; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
  • Lehoux S; Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada. stephanie.lehoux@mcgill.ca.
Sci Rep ; 13(1): 8723, 2023 05 30.
Article in En | MEDLINE | ID: mdl-37253865
Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr-/- chimeras transplanted with bone marrow from Aicda-/- or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr-/-Aicda-/- mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr-/-Aicda-/- compared with Ldlr-/-WT animals. Importantly, Ldlr-/-Aicda-/- mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm2) compared with Ldlr-/-WT (0.30 ± 0.04mm2, P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cytidine Deaminase / Atherosclerosis / Plaque, Atherosclerotic Limits: Animals Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Canada Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cytidine Deaminase / Atherosclerosis / Plaque, Atherosclerotic Limits: Animals Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Canada Country of publication: United kingdom